The proposed research is aimed at using self-stimulation behavior as an animal model to study neural systems related to human affective behavior. To accomplish this goal, we will manipulate the functioning of the reward system of the brain by administering mood-altering drugs with particular emphasis on amphetamine. We have already shown that tolerance develops to amphetamine's facilitation of self-stimulation behavior but not of other behaviors, suggesting that this behavior reflects the mood-altering aspect of the drug's action. In addition, withdrawal of the drug results in a decrease in self-stimulation responding perhaps corresponding to the withdrawal depression reported by humans. Thus, studying the biochemical and anatomical bases of amphetamine's effects on self-stimulation responding should potentially provide important information concerning the physiological bases of affective changes in humans. Such information will be obtained in general by determining the effects of anatomical, behavioral and pharmacological manipulations on self-stimulation responding, on amphetamine's facilitation of that responding on the changes in reward system functioning that occur following chronic amphetamine administration. In addition, we will test whether amphetamine or reserpine-induced depression of self-stimulation might serve as an animal model of the clinical disorder of depression by determining whether antidepressant drugs and electroconvulsive shock will facilitate the recovery from such depressed responding.